Ascites and Spontaneous Bacterial Peritonitis

1. Ascites and Spontaneous Bacterial Peritonitis Arnulf Ferlitsch Associate Professor of Medicine Gastroenterology and Hepatology Medical University of Vienna Banja Luka, Sept. 26th 2009

2. Ascites in Liver Cirrhosis Liver cirrhosis: No 10 ranked cause of death in Europe (3rd in male) Acites: Most common complication of liver cirrhosis 50% of patients with compensated cirrhosis develop ascites within 10 years Most common complication leading to hospital admission

3. Ascites: Diagnosis Physical examination Sonography Puncture / Paracentesis: Blood count and differential ChemistryCytology Culture in blood culture bottles Sensitivity 50 - > 80% when neutrophils > 250  No substitution when INR<2,5 and Thrombocytes > 20000

4. Ascites: Staging International Ascites Club, Hepatology 2003; 38: 258 Grade 1: only detectable by Sonography Grade 2: medium symmetric Distension of the Abdomen Grade 3: massive Ascites with severe abdominal Distension Refractory Ascites: : 5 – 10% of all cases Cannot be mobilised or Early recurrence not preventable by medical therapy Resistant to diuretics Intolerant to diuretics Hepatorenal Syndrome Type II, Hyponatriemia

5. Therapy of Ascites: Standards Grade I: No Therapy or Sodium (Na+) restriction (2.5 g = 90 mmol/d) Grade II: Sodium restriction + Diuretics:  Spironolactone up to 400mg /d : Start 100mg /day followed by Furosemide up to 160mg /d: Start 40mg/day oral  Gut 2009: Combined Start better than Spironolactone followed by Furosemide; response 76 vs 56 % ! Grade III:Paracentesis + Diuretics + Sodium restriction? Volume expansion ? albumin preferred ? when paracentesis >5 L

6. Refractory Ascites: DefinitionInternational Ascites Club, Hepatology 2003; 38: 258 Duration of therapy: min 1 Week Sodium Restriction < 90 mmol / d (~ 2.5 g NaCl / d) Intensive diuretic Therapy (max. Spironolactone 400 mg / d + Furosemid 160 mg / d) No response: <0.8 kg weight loss within 4 days + Na+-Elimination < Na+-Intake Early recurrence of ascites: Recurrence of Grade 2 / 3 Ascites < 4 weeks after Parascentesis and diuretic therapy Complications due to diuretics: hepatic Encephalopathy Renal Failure (Creatinin-increase >100% or more >2 mg/dL) Hyponatriemia (Na+-drop >10 mmol/L or less than <125 mmol/L) K+- derangement (<3 mmol/L or >6 mmol/L)

7. Refractory Ascites: Therapy Paracentesis + ? Volume expansion (Albumin) + Sodium restriction < 90 mmol / d (~ 2.5 g Salz / d) + intensive diuretic therapy (spironolactone 400 mg / d + furosemide 160 mg / d) TIPS Parascentesis > 1 x / 4 weeks Complications due to diuretic therapy (Renal failure, Hyponatriemia) Child Pugh Score < 11 No SBP (Neutrophil count in Ascites < 250 / µL) No spontaneus episodes of hepatic encephalopathy Livertransplantation (OLT) contraindications for TIPS, no contraindications for OLT

8. Metaanalysis TIPS for refractory AscitesSalerno et al., GE 2007; 133: 825 Analysis of 4 RCT‘s TIPS vs. Paracentesis TIPS: uncoated Stent in all Ascites related TIPS Cumulative Survival Survival according to MELD

9. AscitesNew drugs ? Vaptans: (Vaprisol, Astellas) Blocks Antidiuretic Hormon; Vasopressin 2 Receptor-Antagonist In Hyponatriemia, no reduction of mortality in patients with cardiac insufficiency

10. Vaptans: RCT vs PlaceboGines et al, AASLD 2008 139 Patients with Cirrhosis and Hyponatriemia significantly more frequent and faster Na rise Only trends in reduction of ascites and less variceal bleeding

11. Spontaneus -bacterial Peritonitis (SBP) ~20% of all cirrhotic patients with ascites: 50% on admission 50% during in hospital stay Symptoms Fever, abdominal Pain Liver function impairment Hepatic Encephalopathy Renal failure asymptomatic / oligosymptomatic Prognosis 1- / 2- year survival 30-50 / 25-30%

12. SBP: Diagnosis = Puncture !International Ascites Club, J Hepatol 2000; 32: 142 Puncture every cirrhotic patient immediately after admission to the hospital and during hospital stay when having local symptoms Signs of systemic infection Encephalopathy or renal failure GI-Bleeding, before prophylactic AB-therapy Diagnosis Bacterial culture of ascites in blood culture bottles (min. 10mL) (80% vs 50% positve results when neutrophils > 250/µL) Same time blood culture Cell count and differential: Neutrophils in Ascites >250/µL

13. SBP: TherapyInternational Ascites Club, J Hepatol 2000; 32: 142 Empiric Antibiotics when Neutrophils >250/µL often Gram neg- Enterobacteriaceae or non-enteroc. Streptococcus spp. Cephalosporins (3. Gen.; Cefotaxim) or Amoxicillin / Clavulan acid optimal (90% resolution) Albumin (Sort et al., NEJM 1999; 341: 403) 1.5 g / kg immediately + 1 g / kg day 3 Renal failure: significantly lower ? Survival (3 Mo) significantly (50%) ? Puncture after 2 days therapy: Neutrophils ? <25% is non responder to therapy Prophylaxis : Primary / Secondary

14. Secondary Prophylaxis of SBPRimola et al., JHEP 2000; 32: 143 Cirrhotic patients after an SBP-episode Norfloxacin 2 x 400 mg/d continuously SBP-incidence reduced from 68 to 20% Cirrhotic patients with high protein-ascites (>10 g/L) No prophylaxis is required Cirrhotic patients with low-protein ascites (<10 g/dL) No consensus could be reached in 2000 reduced SBP-rate vs. high resistance rate

15. Primary prophylaxis of SBPFernandez et al., GE 2007; 133: 818 Terg et al., JHEP 2008; 48: 774 Fernandez: RCT Norfloxacin 400 mg/d vs. Placebo, 68 Patients Terg: RCT Ciprofloxacin 500 mg/d vs. Placebo, 100 Pat. Defintion: Ascites with Protein <15 g/L; CP =9, Bilirubin =3 mg/dL (Fernandez)

16. 16 Primary prophylaxis of SBPFernandez et al., GE 2007; 133: 818 RCT, Norfloxacin (400 mg qd) vs. Placebo for 1 year Patients Ascites-Protein <15 g/L Advanced liver failure (CP = 9 Punkte or Bilirubin = 3 mg/dL) Renal impairment (Creatinin =1.2 mg/dL or BUN =25 mg/dL or Na+ =130 mmol/L)

17. 17 Summary Ascites:  Combined diuretic therapy: Spironolactone up to 400mg/ day, furosemide up to 160mg /day Spontaneous bacterial peritonitis: Puncture ! Therapy with Cephalosporins or Amoxicillin Prophylaxis with Norfloxacin